Cardiac regeneration in model organisms

Abstract

Myocardial infarction is the most common cause of cardiac injury in humans and results in acute loss of large numbers of myocardial cells. Unfortunately, the mammalian heart is unable to replenish the cells that are lost following a myocardial infarction and an eventual progression to heart failure can often occur as a result. Regenerative medicine based approaches are actively being developed; however, a complete blueprint on how mammalian hearts can regenerate is still missing. Knowledge gained from studying animal models, such as zebrafish, newt, and neonatal mice, that can naturally regenerate their hearts after injury have provided an understanding of the molecular mechanisms involved in heart repair and regeneration. This research offers novel strategies to overcome the limited regenerative response observed in human patients.

Figure 1

Summary of events during regeneration following cryoinjury in zebrafish. In Chablais et al. [52] cryoinjury of about 20 % of the ventricle induces massive cardiac cell death in the injury area and inflammation at 1-day postcryoinjury (dpc). At 4 dpc myocardium is activated and cardiomyocytes proliferate. At 7 dpc, the dead cells are replaced by a collagen-rich fibrotic scar and a fibrin layer takes place along the inner side of the injury area. At 14 dpc the fibrosis resolves gradually as the cardiomyocytes renewal. At 21 dpc the fibrin layer is strongly reduced. At 30 dpc the fibrosis is almost resolved and at 60 dpc the ventricle is completely regenerated with a normal systolic function. In Gonzalez-Rosa et al. [53] the processes from 1–14 dpc are similar to what are described in Chablais et al. Cryoinjury induces a massive cell death at 1 dpc. At 3 dpc the myocardium is activated and proliferating and a collagen-rich fibrotic scar replaced the dead cells at 7 dpc. At 21 dpc only a few cells remain proliferating in myocardium and the scar is at a more luminal position. However, unlike Chablais’ model, the fibrosis starts resolving from 21 dpc and still persists at 90 dpc. At 130 dpc the heart has fully regenerated, although adopted a rounder shape, leading to limited contractility of the ventral part of the ventricle. A atrium, BA bulbus arteriosus, V ventricle.